The present invention relates in general to controlling microorganisms and more particularly relates to microbicides which are preferably environmentally friendly and non-toxic to mammals and which are highly effective against viruses, amoebea, bacteria (both gram-negative and -positive), fungi, algae, spores, yeast, and the like.
Water is the most important element of life since it comprises almost 80% of the human body. In addition, food hygiene depends solely on water, and therefore contamination of water is a common vehicle for the transport of epidemic diseases to humans like Typhoid, food poisoning, and Dysentery. For example, Psychrophilic bacteria""s presence in the micro-flora in water can affect refrigerated food and spoil it. Hence, water contamination cannot be overlooked and extreme measures should be taken to assure a high quality of water to sustain life.
With the advent of technology, clean water is becoming a scarce commodity. Water contamination is unequivocally becoming a worldwide problem with unknown ramifications, and billions of US dollars are spent annually to improve its quality. Contamination of waters is not only restricted to industrialized countries, but includes developing nations as well. Therefore, there is an immediate need to find poignant solutions to maintain and preserve water sources.
Recently, there has been a growing interest among scientists and engineers to develop new water and food disinfectant technologies to clean water from dangerous microorganisms. Various methods have been employed which are divided into two categories; namely, physical, chemical, or both. The physical category is represented by techniques utilizing ultrafiltration, reverse osmosis, radiation, freezing, heating, and ultrasound. Although these methods have proved to be effective, the drawbacks include the large electricity requirements and expensive equipment. On the other hand, the chemical category relies on the use of chemical adjuvants which exhibit biocidal properties such as aldehydes, phenols, alcohol, potassium permanganate, and chlorine and certain chlorine containing compounds. Some of these chemicals have many disadvantages associated with them and are now considered poisonous compounds. For instance, people coming into contact with these substances can develop skin irritation and suffer from long time illnesses which in some cases can be fatal; not to mention the unpleasant taste and odor associated with these chemicals. In addition, formation of mutagenic and carcinogenic agents, and genetic resistance are also some of their disadvantages. Notwithstanding, such compounds have afforded a way to battle these harmful microorganisms and their effectiveness have been unequivocally demonstrated.
Other methods have relied upon the use of ultra-violet irradiated silver fluoride solutions containing silver as a source of germicide activities, such as U.S. Pat. No. 3,422,183, incorporated herein in its entirety by reference. However, such techniques require expensive equipment and large amounts of electricity.
Hydrogen peroxide is a strong oxidizing agent, and it has been used for the past 40 years as a disinfectant. Its main advantage is that it does not produce toxic residue or by-products. It has been used ubiquitously as an indirect food additive, as a disinfectant in hospitals, as a decontamination and purification agent of industrial waste water, and as a cleaning agent for exhaust air. Nonetheless, it decomposes readily to form water and oxygen, and has high sensitivity to sunlight and UV rays. Therefore, it is not suited for long-term use since recontamination cannot be circumvented.
In 1880, the Swiss botanist Carl van Nageli observed that highly diluted silver solutions have an algicidal effect. To describe this effect he coined the term xe2x80x9cOligodynamicxe2x80x9d. Colloidal silver, which is a pure, all-natural substance consisting of sub-microscopic clusters of silver ions held in suspension in de-ionized water by tiny positive charges on the silver ions, is a powerful prophylactic antibiotic which was used for years with no known side effects. It acts as an inhibitor disabling particular enzymes which bacteria, fungi, and viruses used in their mode of metabolism.
Based on this oligodynamic property, U.S. Pat. No. 4,915,955, incorporated in its entirety herein by reference, combines the germicidal effects of hydrogen peroxide with silver, an inorganic acid, and an organic stabilizer at concentrations of 10-35 mg/l to combat many forms of bacteria and viruses. The process is based on silver ions, with the aid of hydrogen peroxide, damaging the protective biofilms of these microorganisms. Hence, this method depends solely on killing germs intercellularly. Accordingly, there is a need to develop a new generation of microbicidal agents that overcome one or more of the above-described disadvantages.
International Published Patent Application No. WO 00/62618 describes the formation of metal complexes suitable as disinfectants and sanitizers to combat pathogenic microorganisms. It relies on using metal ions and amino acids to form complexes, which serve as carriers for metals, in order to diffuse into the intra-cellular medium of such microorganisms where it exhibits its biocidal activities. The composition can be prepared by mixing a metal salt compound in an aqueous solution, and an inorganic acid at room temperature to adjust the pH of the solution; adding at least on an equimolar basis, depending on the valency of the metals, at least one amino acid to form an insoluble metal complex while homogenizing the mixture; and depending on its use, the resultant solution can then be proportioned with various ratios to make suitable disinfectants either by adding appropriate amount of distilled-deionized water and/or by the addition of chlorhexidine gluconate, chlorhexidine digluconte, chlorhexidine dihydrochloride, chlorhexidine diacetate, isopropanol, and hydrogen peroxide. According to a preferred embodiment, silver nitrate is used as the metal salt; distilled deionized water is used to make up the aqueous medium; phosphoric acid is used as the inorganic acid; glutamic acid is used as the amino acid; and hydrogen peroxide is used as the synergetic disinfectant.
The present invention relies on using metal ions (M). A chemical matrix or complex is formed from metal ions and potassium sodium tartrate used in at least one fourth (xc2xc) of the stoichiometric amount of the metal ion, depending on the valency of the metal. These concentrated complexes can then be mixed with water to form suitable disinfectants.
A particularly useful application of the disinfectant of the present invention is in the preservation of flowers and plants, as a general disinfectant, sterilization of articles and surfaces and areas, including, but not limited to, food, liquids, (e.g., water, beverages), animal feed, pharmaceuticals, hospitals, surgical equipment, swimming pools, saunas, fish, poultry, cattle, and other farming uses, and the like.
It is to be understood that the preceding general discussion and the discussion which follows are considered explanatory and exemplary in nature, and are solely intended to give additional merits of the current invention, as claimed.
The present invention provides a suitable concentrate of organo-metal compounds that form suitable disinfectants upon admixing with water or other aqueous sources. The basic principle that governs the formation of such a concentrate is the fact that the metal ions are complexed with potassium sodium tartrate (hereinafter xe2x80x9cPSTxe2x80x9d). The PST or ion thereof is used in at least one-fourth of the stoichiometric amounts or more (based on the metal ion present) to form organic complexes.
To enhance its activity, the concentrated organic complex can be mixed with other disinfectants, including, but not limited to, isopropanol, chlorhexidine gluconate, chlorhexidine digluconate, chlorhexidine dihydrochloride, chlorhexidine diacetate, and/or hydrogen peroxide, though it is not necessary. In addition, natural and artificial color and flavor additives as well as other additives can be added as well.
Of course, the microbicidal formulations of the present invention can be used either directly, by introduction to a system, e.g., a swimming pool, or can be diluted with aqueous solutions, like distilled and/or deionized water to provide the necessary biocidal activity, depending on the application.
With respect to the organic complex, the metal ion(s) complexes with potassium sodium tartrate (hereinafter xe2x80x9cPST-Mxe2x80x9d).
Other organic complexes can be used in addition to or in combination with the PST-M complex such as the R-M complexes described in International Published Patent Application No. WO 00/62618, incorporated in its entirety by reference herein. When additional complexes are used, the R group may also include at least one amino acid or can be formed from at least one amino acid. The amino acids are preferably amphoteric, that is, they can react either as acids or as bases, depending on the circumstances. Preferably, examples of amino acids or compounds containing amino acids which can be used as the R group or to form the R group include, but are not limited to, xcex1-amino acids. Specific examples include, but are not limited to, isoleucine, phenylalanine, leucine, lysine, methionine, threonine, tryptophan, valine, alanine, glycine, arginine, histidine, hydroxyproline, xcex1-aminobutyric acid, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, phenylalanine, proline, serine, tyrosine, and derivatives thereof and mixtures thereof.
The complex of the present invention is preferably accomplished by forming the complex under low pH conditions (e.g., acidic conditions) and preferably at pH conditions of pH 2.0 or less and more preferably at a pH 1.5 or less.
With respect to the other part of the complex which is M, M represents at least one monovalent or polyvalent metal ion or cation, which is microbicidal to at least one microorganism. Preferably, the metal ion is microbicidal to a multitude of microorganisms. Examples of the metal ion include, but are not limited to, cations of silver including colloidal silver, copper, zinc, mercury, manganese, chromium, nickel, cadmium, arsenic, cobalt, aluminum, lead, selenium, platinum, gold, titanium, tin, barium, bismuth, vanadium, iron, strontium, antimony, and the like.
Optionally, the PST in the complex of the present invention can replace partially or entirely the amino acid group in the R-M complex described above. The composition thus obtained is suitable as a disinfectant. By using the PST, the resulting composition preferably potentiates the effect of controlling pathogenic microorganisms. By potentiating the microbicidal compositions of the present invention, lower concentrations of heavy metals can then be used to achieve a certain efficacy. Accordingly, the use of the PST and the like preferably reduces any possible detrimental and deleterious effects of these metals on the environment.
PST inhibits crystal growth and dendrites formation in metal electrodeposition; hence, the formation of smooth coherent metal surfaces is favorable. Froment, M., et al. xe2x80x9cInfluence du Tartrate Double de Sodium et de Potassium sur la Croissance des Depots Electrolytiques D""argent Obtenus a Partir d""une Solution Aqueuse de Nitratexe2x80x9d Comptes Rendus de L""academie des Science, Paris, t271C, pp. 253-256 (1970), incorporated in its entirety by reference herein. PST forms coherent complexes in the present invention so it can bound to silver or other metals, precluding the formation of silver crystals. The amount of the PST used in the preparation of the solution can vary, depending on the metal and the acid being used. Preferably, not more than one fourth of the equimolar portion of the PST with respect to the metal is preferably used, depending on the valency of the metal.
Thus, the PST containing microbicidal compositions of the present invention can be prepared in the same manner and are as effective, except that some or all of the amino acid groups are replaced by the PST. The PST containing microbicidal formulation can be prepared by dissolving at least one metal salt with at least one inorganic acid in an aqueous medium, and then adding the PST in its designated amount. The composition provided here may be prepared from various complexes that may form together a more complicated complex and/or complexes. The aqueous solution obtained may be concentrated and dried, and the concentrate can be made as a gel or as a solid in different forms using conventional methods available to those skilled in the art. The amount of PST used in the preparation of the solution can vary, depending on the metal and the optional amino acid being used. Preferably, not more than one fourth the equimolar portion of PST with respect to the metal should be used, depending on the valency of the metal. Preferably, slightly in excess of one fourth of the amount for univalent metal ions (e.g., Ag); at least twice as much (half) for bivalent metals (e.g. Cu), and so on. Any source of ionic M in the form of salts can be used in the present invention. For the case of silver, colloidal silver can be used as well.
Thus, the complex of the present invention can be prepared by forming the metal ion from at least one metal salt compound and PST. In the preferred process of making the organic complex of the present invention, a metal salt compound is mixed with PST alone or with at least one amino acid at room temperature (e.g., 20-30xc2x0 C.) and preferably in the presence of an aqueous solution like a distilled-deionized water. Then, the organic containing compound such as PST alone or with amino acid forms the metal complex preferably while homogenizing the mixture. This preparation preferably occurs under low pH conditions, such as pH of about 2.0 or less and more preferably at a pH of 1.5 or less. The resulting solution can then be further diluted with aqueous solution and preferably distilled-deionized water and further disinfectants or other additives can be added to form the microbicidal compositions of the present invention. The aqueous solution may be condensed and dried using conventional methods available to those skilled in the art to produce gels as well as solids, such as tablets or powders.
According to the present invention, controlling the growth of at least one microorganism includes both the reduction and/or prevention of such growth. It is to be further understood that by xe2x80x9ccontrolling,xe2x80x9d the growth of at least one microorganism is inhibited. In other words, there is no growth or substantially no growth of at least one microorganism. xe2x80x9cControllingxe2x80x9d the growth of at least one microorganism includes maintaining a microorganism population at a desired level (including undetectable levels such as zero population), reducing a microorganism population to a desired level, and/or inhibiting or slowing the growth of at least one microorganism. Thus, materials and mediums susceptible to attack by at least one microorganism are preserved and/or protected from this attack and the resultant deleterious effects. The present invention also provides a method for controlling the growth of at least one microorganism in or on a material or medium susceptible to attack by the microorganism which comprises the step of adding to the material or medium a composition of the present invention in an amount effective to control the growth of the microorganism.
The mode as well as the rates of application of the composition of this invention could vary depending upon the intended use. The composition could be applied by spraying or brushing onto the material or product. The material or product in question could also be treated by dipping in a suitable formulation of the composition. In a liquid or liquid-like medium, the composition could be added into the medium by pouring or by metering with a suitable device so that a solution or dispersion of the composition can be produced. Thus, the substrates or materials susceptible to attack by these types of microorganisms are preserved from this attack and the resulting spoilage or other detrimental effects caused by the microorganisms. Further, it is to be understood that xe2x80x9ccontrollingxe2x80x9d the growth of at least one microorganism also includes biostatically reducing and/or maintaining a low level of microorganisms such that the attack by microorganisms and any resulting spoilage or other detrimental effects are mitigated, i.e., the microorganism growth rate or microorganism attack rate is slowed down or eliminated.
Microorganisms, as used herein, include, but are not limited to bacteria, both gram-positive and -negative, fungi, algae, viruses, amoebae, spores, and the like, and include both yeast and molds.
The biocides or microbicidal compositions of the present invention described herein have a plethora of applications and uses. They are suitable for the sterilization of drinking water, suitable for the beverage and food industry, suitable for sterilizing exposed surfaces, exhaust air and ventilation components, animal feed, suitable for use in the pharmaceutical industry, in hospitals, for surgical equipment, in swimming pools, in saunas, and for fish, poultry, and cattle farming, and the like.
The present invention is also effective in controlling biofouling. The microbicidal formulations of the present invention can be introduced directly into the source of where the biofouling is occurring or can be mixed with aqueous solutions and introduced into the area where biofouling is occurring.
Another beneficial use of the present invention is with respect to preserving or extending the life of flowers and plants. The present invention can be used as a preservative for cut flowers and cut plants by including the formulation of the present invention in the water in which the cut flowers or plants are placed into or can be formulated into a powder or tablet which can be introduced into the container holding the cut flowers or plants. Also, the formulations of the present invention can be used as a spray which is applied to living plants and flowers and acts as an agent to control pests, insects, and/or microorganisms and thus preserves a living plant and protects the plant from plant diseases, bacteria, viruses, fungus, algae, insects, and the like. The amount of the formulation which is used depends upon the plant or flowers and as described above, is typically a diluted aqueous formulation containing the microbicidal compositions of the present invention.
The present invention is further illustrated by the following non-limiting examples. These experiments constitute some of the embodiments of the invention herein disclosed. After the preparation of these disinfectants, their efficacy was then tested and evaluated against a highly resistant strain of Pseudomonas Aeruginosa.